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Article ; Online: ClinGen's Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents.

Genetics in medicine : official journal of the American College of Medical Genetics

2022 Volume 24, Issue 6, Page(s) 1328–1335

Abstract: Purpose: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children ... ...

Abstract	Purpose: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG). Methods: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs. Modification of the adult framework for the pediatric setting included accounting for special considerations for reporting presymptomatic or predictive genetic findings in the pediatric context, such as maintaining future autonomy by not disclosing conditions not actionable until adulthood. The Pediatric AWG then applied this new framework to genes and associated conditions with putative actionability. Results: As of September 2021, the Pediatric AWG applied the new framework to 70 actionability topics representing 143 genes. Reports and scores are publicly available at www.clinicalgenome.org. Conclusion: The Pediatric AWG continues to curate gene-condition topics and build an evidence-based resource, supporting clinical communities and decision-makers with policy development on the return of SFs in pediatric populations.
MeSH term(s)	Adolescent ; Adult ; Child ; Chromosome Mapping ; Genetic Testing ; Humans ; Research Report
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1455352-1
ISSN	1530-0366 ; 1098-3600
ISSN (online)	1530-0366
ISSN	1098-3600
DOI	10.1016/j.gim.2022.02.019
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Article ; Online: Infective endocarditis due to Granulicatella adiacens: a case report and review.

Padmaja, Kanne / Lakshmi, Vemu / Subramanian, Sreevdya / Neeraja, Mamidi / Krishna, Siva Rama / Satish, O Sai

Journal of infection in developing countries

2014 Volume 8, Issue 4, Page(s) 548–550

Abstract: Infective endocarditis (IE) caused by nutritionally variant Streptococci (NVS) is associated with high bacteriologic and treatment failure and mortality rates compared to endocarditis caused by other Streptococci. With automated blood culture systems, ... ...

Abstract	Infective endocarditis (IE) caused by nutritionally variant Streptococci (NVS) is associated with high bacteriologic and treatment failure and mortality rates compared to endocarditis caused by other Streptococci. With automated blood culture systems, the rates of NVS-associated IE accounts for 5%-6% cases. We report a case of IE caused by NVS in an elderly female patient with no risk factors. The patient was successfully treated with combination antimicrobial therapy.
MeSH term(s)	Carnobacteriaceae/isolation & purification ; Endocarditis, Bacterial/drug therapy ; Endocarditis, Bacterial/microbiology ; Female ; Gram-Positive Bacterial Infections/drug therapy ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Middle Aged
Language	English
Publishing date	2014-04-15
Publishing country	Italy
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2394024-4
ISSN	1972-2680 ; 2036-6590
ISSN (online)	1972-2680
ISSN	2036-6590
DOI	10.3855/jidc.3689
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Article ; Online: ClinGen Variant Curation Interface: a variant classification platform for the application of evidence criteria from ACMG/AMP guidelines.

Preston, Christine G / Wright, Matt W / Madhavrao, Rao / Harrison, Steven M / Goldstein, Jennifer L / Luo, Xi / Wand, Hannah / Wulf, Bryan / Cheung, Gloria / Mandell, Mark E / Tong, Howard / Cheng, Shaung / Iacocca, Michael A / Pineda, Arturo Lopez / Popejoy, Alice B / Dalton, Karen / Zhen, Jimmy / Dwight, Selina S / Babb, Lawrence /

DiStefano, Marina / O'Daniel, Julianne M / Lee, Kristy / Riggs, Erin R / Zastrow, Diane B / Mester, Jessica L / Ritter, Deborah I / Patel, Ronak Y / Subramanian, Sai Lakshmi / Milosavljevic, Aleksander / Berg, Jonathan S / Rehm, Heidi L / Plon, Sharon E / Cherry, J Michael / Bustamante, Carlos D / Costa, Helio A

Genome medicine

2022 Volume 14, Issue 1, Page(s) 6

Abstract: Background: Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive ... ...

Abstract	Background: Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome and interpreting genetic variants to inform healthcare management have been lacking. Results: Here we present the ClinGen Variant Curation Interface (VCI), a global open-source variant classification platform for supporting the application of evidence criteria and classification of variants based on the ACMG/AMP variant classification guidelines. The VCI is among a suite of tools developed by the NIH-funded Clinical Genome Resource (ClinGen) Consortium and supports an FDA-recognized human variant curation process. Essential to this is the ability to enable collaboration and peer review across ClinGen Expert Panels supporting users in comprehensively identifying, annotating, and sharing relevant evidence while making variant pathogenicity assertions. To facilitate evidence-based improvements in human variant classification, the VCI is publicly available to the genomics community. Navigation workflows support users providing guidance to comprehensively apply the ACMG/AMP evidence criteria and document provenance for asserting variant classifications. Conclusions: The VCI offers a central platform for clinical variant classification that fills a gap in the learning healthcare system, facilitates widespread adoption of standards for clinical curation, and is available at https://curation.clinicalgenome.org.
MeSH term(s)	Humans ; Genetic Testing ; Genetic Variation ; Genome, Human ; Genomics
Language	English
Publishing date	2022-01-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-021-01004-8
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Article ; Online: PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

Koc, Soner / Lloyd, Michael W / Grover, Jeffrey W / Xiao, Nan / Seepo, Sara / Subramanian, Sai Lakshmi / Ray, Manisha / Frech, Christian / DiGiovanna, John / Webster, Phillip / Neuhauser, Steven / Srivastava, Anuj / Woo, Xing Yi / Sanderson, Brian J / White, Brian / Lott, Paul / Dobrolecki, Lacey E / Dowst, Heidi / Evrard, Yvonne A /

NAR cancer

2022 Volume 4, Issue 2, Page(s) zcac014

Abstract: We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available ... ...

Abstract	We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials.
Language	English
Publishing date	2022-04-22
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcac014
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Article ; Online: ClinGen Variant Curation Interface

Christine G. Preston / Matt W. Wright / Rao Madhavrao / Steven M. Harrison / Jennifer L. Goldstein / Xi Luo / Hannah Wand / Bryan Wulf / Gloria Cheung / Mark E. Mandell / Howard Tong / Shaung Cheng / Michael A. Iacocca / Arturo Lopez Pineda / Alice B. Popejoy / Karen Dalton / Jimmy Zhen / Selina S. Dwight / Lawrence Babb /

Marina DiStefano / Julianne M. O’Daniel / Kristy Lee / Erin R. Riggs / Diane B. Zastrow / Jessica L. Mester / Deborah I. Ritter / Ronak Y. Patel / Sai Lakshmi Subramanian / Aleksander Milosavljevic / Jonathan S. Berg / Heidi L. Rehm / Sharon E. Plon / J. Michael Cherry / Carlos D. Bustamante / Helio A. Costa / on behalf of the Clinical Genome Resource (ClinGen)

Genome Medicine, Vol 14, Iss 1, Pp 1-

a variant classification platform for the application of evidence criteria from ACMG/AMP guidelines

2022 Volume 12

Abstract: Abstract Background Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible ... ...

Abstract	Abstract Background Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome and interpreting genetic variants to inform healthcare management have been lacking. Results Here we present the ClinGen Variant Curation Interface (VCI), a global open-source variant classification platform for supporting the application of evidence criteria and classification of variants based on the ACMG/AMP variant classification guidelines. The VCI is among a suite of tools developed by the NIH-funded Clinical Genome Resource (ClinGen) Consortium and supports an FDA-recognized human variant curation process. Essential to this is the ability to enable collaboration and peer review across ClinGen Expert Panels supporting users in comprehensively identifying, annotating, and sharing relevant evidence while making variant pathogenicity assertions. To facilitate evidence-based improvements in human variant classification, the VCI is publicly available to the genomics community. Navigation workflows support users providing guidance to comprehensively apply the ACMG/AMP evidence criteria and document provenance for asserting variant classifications. Conclusions The VCI offers a central platform for clinical variant classification that fills a gap in the learning healthcare system, facilitates widespread adoption of standards for clinical curation, and is available at https://curation.clinicalgenome.org
Keywords	Variant curation ; Precision medicine ; Clinical genetics ; Clinical Genome Resource Consortium ; Medicine ; R ; Genetics ; QH426-470
Subject code	020
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amino-functionalised mesoporous silica microspheres for immobilisation of

Saikia, Kongkona / Senthil Kumar, Ponnusamy / Karanam Rathankumar, Abiram / SaiLavanyaa, Sundar / Srinivasan, Lakshmi / Subramanian, Sivanesan / Cabana, Hubert / Gosselin, Mathilde / Vinoth Kumar, Vaidyanathan

IET nanobiotechnology

2022 Volume 14, Issue 8, Page(s) 732–738

Abstract: In the present study, amino-functionalised mesoporous silica microspheres were utilised as support for the covalent immobilisation ... ...

Abstract	In the present study, amino-functionalised mesoporous silica microspheres were utilised as support for the covalent immobilisation of
MeSH term(s)	Amino Acids/chemistry ; Biocatalysis ; Dicarboxylic Acids/chemistry ; Dicarboxylic Acids/metabolism ; Enzymes, Immobilized/chemistry ; Enzymes, Immobilized/metabolism ; Fungal Proteins/chemistry ; Fungal Proteins/metabolism ; Furans/chemistry ; Furans/metabolism ; Green Chemistry Technology ; Lipase/chemistry ; Lipase/metabolism ; Microspheres ; Silicon Dioxide/chemistry
Chemical Substances	Amino Acids ; Dicarboxylic Acids ; Enzymes, Immobilized ; Fungal Proteins ; Furans ; 2,5-furandicarboxylic acid (73C4JJ695C) ; Silicon Dioxide (7631-86-9) ; Lipase (EC 3.1.1.3) ; lipase B, Candida antarctica (EC 3.1.1.3)
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2264529-9
ISSN	1751-875X ; 1751-8741
ISSN (online)	1751-875X
ISSN	1751-8741
DOI	10.1049/iet-nbt.2020.0021
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Article ; Online: Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs.

Amin, Viren / Harris, R Alan / Onuchic, Vitor / Jackson, Andrew R / Charnecki, Tim / Paithankar, Sameer / Lakshmi Subramanian, Sai / Riehle, Kevin / Coarfa, Cristian / Milosavljevic, Aleksandar

Nature communications

2015 Volume 6, Page(s) 6370

Abstract: Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics ... ...

Abstract	Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, we determine tissue-specific epigenetic regulation for 3,753 (69% examined) lincRNAs, with 54% active in one of the 14 cell/tissue clusters and an additional 15% in two or three clusters. A larger fraction of lincRNA TSSs is marked in a tissue-specific manner by H3K4me1 than by H3K4me3. The tissue-specific lincRNAs are strongly linked to tissue-specific pathways and undergo distinct chromatin state transitions during cellular differentiation. Polycomb-regulated lincRNAs reside in the bivalent state in embryonic stem cells and many of them undergo H3K27me3-mediated silencing at early stages of differentiation. The exquisitely tissue-specific epigenetic regulation of lincRNAs and the assignment of a majority of them to specific tissue types will inform future studies of this newly discovered class of genes.
MeSH term(s)	Cell Differentiation ; Embryonic Stem Cells/physiology ; Epigenesis, Genetic ; Epigenomics ; Humans ; Organ Specificity ; Phenotype ; Polycomb-Group Proteins/physiology ; RNA, Long Noncoding/metabolism ; Regulatory Elements, Transcriptional
Chemical Substances	Polycomb-Group Proteins ; RNA, Long Noncoding
Language	English
Publishing date	2015-02-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/ncomms7370
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Article: Integration of extracellular RNA profiling data using metadata, biomedical ontologies and Linked Data technologies.

Subramanian, Sai Lakshmi / Kitchen, Robert R / Alexander, Roger / Carter, Bob S / Cheung, Kei-Hoi / Laurent, Louise C / Pico, Alexander / Roberts, Lewis R / Roth, Matthew E / Rozowsky, Joel S / Su, Andrew I / Gerstein, Mark B / Milosavljevic, Aleksandar

Journal of extracellular vesicles

2015 Volume 4, Page(s) 27497

Abstract: The large diversity and volume of extracellular RNA (exRNA) data that will form the basis of the exRNA Atlas generated by the Extracellular RNA Communication Consortium pose a substantial data integration challenge. We here present the strategy that is ... ...

Abstract	The large diversity and volume of extracellular RNA (exRNA) data that will form the basis of the exRNA Atlas generated by the Extracellular RNA Communication Consortium pose a substantial data integration challenge. We here present the strategy that is being implemented by the exRNA Data Management and Resource Repository, which employs metadata, biomedical ontologies and Linked Data technologies, such as Resource Description Framework to integrate a diverse set of exRNA profiles into an exRNA Atlas and enable integrative exRNA analysis. We focus on the following three specific data integration tasks: (a) selection of samples from a virtual biorepository for exRNA profiling and for inclusion in the exRNA Atlas; (b) retrieval of a data slice from the exRNA Atlas for integrative analysis and (c) interpretation of exRNA analysis results in the context of pathways and networks. As exRNA profiling gains wide adoption in the research community, we anticipate that the strategies discussed here will increasingly be required to enable data reuse and to facilitate integrative analysis of exRNA data.
Language	English
Publishing date	2015-08-28
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	2683797-3
ISSN	2001-3078
ISSN	2001-3078
DOI	10.3402/jev.v4.27497
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Article ; Online: Integration of extracellular RNA profiling data using metadata, biomedical ontologies and Linked Data technologies

Sai Lakshmi Subramanian / Robert R. Kitchen / Roger Alexander / Bob S. Carter / Kei-Hoi Cheung / Louise C. Laurent / Alexander Pico / Lewis R. Roberts / Matthew E. Roth / Joel S. Rozowsky / Andrew I. Su / Mark B. Gerstein / Aleksandar Milosavljevic

Journal of Extracellular Vesicles, Vol 4, Iss 0, Pp 1-

2015 Volume 6

Abstract	The large diversity and volume of extracellular RNA (exRNA) data that will form the basis of the exRNA Atlas generated by the Extracellular RNA Communication Consortium pose a substantial data integration challenge. We here present the strategy that is being implemented by the exRNA Data Management and Resource Repository, which employs metadata, biomedical ontologies and Linked Data technologies, such as Resource Description Framework to integrate a diverse set of exRNA profiles into an exRNA Atlas and enable integrative exRNA analysis. We focus on the following three specific data integration tasks: (a) selection of samples from a virtual biorepository for exRNA profiling and for inclusion in the exRNA Atlas; (b) retrieval of a data slice from the exRNA Atlas for integrative analysis and (c) interpretation of exRNA analysis results in the context of pathways and networks. As exRNA profiling gains wide adoption in the research community, we anticipate that the strategies discussed here will increasingly be required to enable data reuse and to facilitate integrative analysis of exRNA data.
Keywords	ERC Consortium ; DMRR ; exRNA ; exRNA Atlas ; exRNA Portal ; Biology (General) ; QH301-705.5 ; Science ; Q
Subject code	004
Language	English
Publishing date	2015-08-01T00:00:00Z
Publisher	Co-Action Publishing
Document type	Article ; Online
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Article: exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Murillo, Oscar D / Thistlethwaite, William / Rozowsky, Joel / Subramanian, Sai Lakshmi / Lucero, Rocco / Shah, Neethu / Jackson, Andrew R / Srinivasan, Srimeenakshi / Chung, Allen / Laurent, Clara D / Kitchen, Robert R / Galeev, Timur / Warrell, Jonathan / Diao, James A / Welsh, Joshua A / Hanspers, Kristina / Riutta, Anders / Burgstaller-Muehlbacher, Sebastian / Shah, Ravi V /

Yeri, Ashish / Jenkins, Lisa M / Ahsen, Mehmet E / Cordon-Cardo, Carlos / Dogra, Navneet / Gifford, Stacey M / Smith, Joshua T / Stolovitzky, Gustavo / Tewari, Ashutosh K / Wunsch, Benjamin H / Yadav, Kamlesh K / Danielson, Kirsty M / Filant, Justyna / Moeller, Courtney / Nejad, Parham / Paul, Anu / Simonson, Bridget / Wong, David K / Zhang, Xuan / Balaj, Leonora / Gandhi, Roopali / Sood, Anil K / Alexander, Roger P / Wang, Liang / Wu, Chunlei / Wong, David T.W / Galas, David J / Van Keuren-Jensen, Kendall / Patel, Tushar / Jones, Jennifer C / Das, Saumya / Cheung, Kei-Hoi / Pico, Alexander R / Su, Andrew I / Raffai, Robert L / Laurent, Louise C / Roth, Matthew E / Gerstein, Mark B / Milosavljevic, Aleksandar

Elsevier Inc. Cell. 2019 Apr. 04, v. 177, no. 2

2019

Abstract: To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR ... ...

Abstract	To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.
Keywords	RNA ; blood serum ; case-control studies ; cell communication ; exercise ; hosts ; humans ; lipoproteins ; models ; quantitative polymerase chain reaction ; ribonucleoproteins ; saliva ; urine
Language	English
Dates of publication	2019-0404
Size	p. 463-477.e15.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2019.02.018
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